PRODUCT TESTING ANIMAL CORE (PTAC) PROJECT SUMMARY The Product Testing Animal Core (PTAC) will provide: 1) high-quality gnotobiotic mice, 2) in vivo evaluation of radiomitigators, 3) axenic models of radiation effects, and 4) support regarding animal research issues and regulations. The PTAC's platforms are exceptional because it manages, breeds, and maintains its own mouse colony. For over 30 years, the vivarium has been maintained as an extremely high-quality gnotobiotic facility where animals have a defined microbiota. Performing experiments in mice that are of the highest quality from microbial and genetic standpoints is essential if meaningful results are to be obtained. Further, establishment of an absolutely germfree, or axenic, mouse colony within the gnotobiotic facility has been initiated and the PTAC plans to expand it to accommodate the needs of the CMCR Projects. The involvement of microbes in the maintenance of host physiology and in acute radiation syndrome (ARS) due to bacterial translocation and sepsis, aided and abetted by immunosuppression, has long been discussed. Germfree animals will facilitate the CMRC mission aimed at identifying specific agents or regimens that optimize normal tissue radioresistance by eliminating a role for microbes in ARS and delayed effects of acute radiation exposure. The facility currently serves approximately 113 investigators working in the fields of radiation, DNA repair, immunology, and cancer. It breeds over 140 strains, 59,000 per year, of normal, immune deficient, and transgenic mice all of which are accessible to CMCR investigators. As part of the pipeline for new drug development, the PTAC, utilizing such in-house animal models, will characterize the pharmacokinetics and examine the radiomitigative efficacy of compounds screened from the Product Development Core (PDC). Absorption, distribution, metabolism, and excretion (ADME) assessments will be carried out on potential drug candidates in conjunction with the PDC. Subsequently, the PTAC will use well-characterized preclinical animal models to test compounds for their ability to mitigate radiation-induced damage in vivo. Furthermore, because ARS is a multi-organ phenomenon, focus on single systems will not necessarily reflect the total effect of a potential mitigator in the context of the organism. Accordingly, the PTAC will exploit its extensive experience with the effects of ionizing radiation on multiple normal tissues (bone marrow, intestine, lung, skin, kidney, brain, and spinal cord) at the molecular, cellular, and whole tissue level. Finally, like all facilities at UCLA, the PTAC-associated colony is fully AAALAC- accredited and is the jewel in the crown of the mouse establishments at UCLA with a long history of cooperation with the IACUC. The PTAC will perform a vital function in facilitating animal research within the CMRC, integrating the Projects, standardizing information derived from individual studies, and enabling development of viable new drugs for imminent future clinical investigation to meet the CMCR mission.